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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/16911

Title: Matrix metalloproteinases as therapeutic targets in protozoan parasitic infections
Authors: Geurts, Nathalie
OPDENAKKER, Ghislain
Van den Steen, Philippe E.
Issue Date: 2012
Publisher: PERGAMON-ELSEVIER SCIENCE LTD
Citation: PHARMACOLOGY & THERAPEUTICS, 133 (3), p. 257-279
Abstract: Matrix metalloproteinases (MMPs) are associated with processes of tissue remodeling and are expressed in all infections with protozoan parasites. We here report the status of MMP research in malaria, trypanosomiasis, leishmaniasis and toxoplasmosis. In all these infections, the balances between MMPs and endogenous MMP inhibitors are disturbed, mostly in favor of active proteolysis. When the infection is associated with leukocyte influx into specific organs, immunopathology and collateral tissue damage may occur. These pathologies include cerebral malaria, sleeping sickness (human African trypanosomiasis), Chagas disease (human American trypanosomiasis), leishmaniasis and toxoplasmic encephalitis in immunocompromised hosts. Destruction of the integrity of the blood-brain barrier (BBB) is a common denominator that may be executed by leukocytic MMPs under the control of host cytokines and chemokines as well as influenced by parasite products. Mechanisms by which parasite-derived products alter host expression of MMP and endogenous MMP inhibitors, have only been described for hemozoin (Hz) in malaria. Hence, understanding these interactions in other parasitic infections remains an important challenge. Furthermore, the involved parasites are also known to produce their own metalloproteinases, and this forms an extra stimulus to investigate MMP inhibitory drugs as therapeutics. MMP inhibitors (MMPIs) may dampen collateral tissue damage, as is anecdotically reported for tetracyclines as MMP regulators in parasite infections.
Notes: [Geurts, Nathalie; Opdenakker, Ghislain; Van den Steen, Philippe E.] Univ Leuven, Rega Inst Med Res, Immunobiol Lab, B-3000 Louvain, Belgium.
URI: http://hdl.handle.net/1942/16911
DOI: 10.1016/j.pharmthera.2011.11.008
ISI #: 000301217700001
ISSN: 0163-7258
Category: A1
Type: Journal Contribution
Appears in Collections: Research publications

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